The long-range objective of the proposed research is to determine the cellular and molecular developmental events that lead to the differentiation of specific cell types in the vertebrate retina. The immediate experimental approach toward this goal is to focus on the role of hh genes in retinal development in teleost fish. Five specific aims are proposed: (1) to characterize the spatiotemporal expression of hh genes in the retinal pigmented epithelium (RPE) of zebrafish; (2) to experimentally reduce expression of hh genes in the RPE of embryonic zebrafish and examine the effects on retinal cell differentiation and patterning; (3) to create sites of precocious and/or ectopic hh expression in the zebrafish eye and examine the effects on retinal cell differentiation and patterning; (4) to examine specific effects of hh protein on rod photoreceptor production in the retina of adult goldfish; and (5) to identify retinal cell types that receive the hh signal by localizing expression of the hh receptor. The proposed research program emphasizes potential involvement of hh gene expression in the process of rod photoreceptor development. A loss of rod photoreceptors is a primary event in a number of hereditary retinal degenerations; the study of genes that may be involved in rod production may ultimately lead to the development of strategies for rod replacement therapy in humans.